VI Reunión Anual de la Sección de insuficiencia Cardiaca y Trasplante 26 y 27 de Junio de 2009 Actividad acreditada por el comité de Acreditación de la Sociedad Española de Cardiología
Antagonistas del receptor de la Adenosina A1: nuevo paradigma en el tratamiento de la IC Aguda. Dr. José Luis López Sendón
1. Disclosure Information: clinical research grants from: BMS, Bayer Jose López-Sendón Hospital Universitario La Paz. Madrid Antagonistas del receptor A1 de Adenosina Nuevo pardigma en el tratamiento de la insuficiencia cardiaca aguda
3. Adams KF et al. Am Heart J. 2005; 149: 209 Cleland JGF et al. Eur Heart J. 2003; 24: 442 Fonarow GC et al. J Am Coll Cardiol. 2005; 45: 345A Hospitalizations for HF: Patient Characteristics ADHERE EURO HF OPTIMIZE-HF (%) (107,920 pts.) (11,327 pts.) (48,612 pts.) Any dyspnea 89 70 90? Dyspnea at rest 34 40 45 Fatigue 32 35 23 Rales 68 N/A 65 Peripheral edema 66 23 65
4. 60-Day All-cause Mortality 0% 10% 20% N = 204 115 (64%) (36%) ACTIVE in CHF Adapted from Gheorghiade M et al. JAMA. 2004;291:1963 Congestion after Initial In-Hospital Therapy is Associated with Higher 60-day Mortality Severe Congestion* 7.8 3.5 No Severe Congestion*
5. Bayliss et al. Br Heart J. 1987; 57: 17 Neurohormonal effect of Diuretics in Heart Failure Basal (n=12) Plasma Renin Activity (ng/mL/h) 50 10 2.5 0.5 P =.0002 After Diur étic (n=11) Plasma Aldosterone (pmol/L) % 1000 600 200 100 P =.0007 Basal (n=12) After Diuretic (n=11)
6. Resistencia a diuréticos Incremento de la Mortalidad y Morbilidad Tratamiento diur ético Insuficiencia renal Disminuci ón de la función renal Desarrollo de Resistencia a Diur éticos Disminuci ón Flujo sanguíneo Activaci ón Neurohormonal
8. Incidencia de IR en IC 43,3% 41,8% Pacientes (nº) FEVI ≥ 50% FEVI < 50% Insuficiencia Renal: TFG < 60 ml/min/1.73m2 Grigorian L, et al . REC 2006:59:99
9. Insuficiencia cardiaca aguda Factores relacionados con Mortalidad intrahospitalaria EHFS-II: n=3432 L ó pez-Send ón et al ECC 2007
11. NA + and H 2 O RETENTION SNS 1 Efferent art. constriction 2 Na + reabs. in prox. tubule Angiotensin 1 Efferent art. constriction 2 Na + reabs. in prox. tubule Aldosterone 3 Reabsorption H 2 O and Na+ 4 K + Secretion Vasopressin 5 H 2 O reabs. in collecting tubule 6 Na + reabs. in ascending branch of the loop of Henle Adenosin 1b A fferent art. constriction 1 Na + reabs. in prox. tubule Atrial Natriuretic P 7 Increase glomerular filtration 8 Na reabs. in collecting tubule Renal Prostaglandins 9 Afferent art. vasodilatation 10 Reduce Na + reabsorption in asc. branch of loop of Henle 11 Inhibit Na + reabsorption in collecting tubule 12 1 2 4 5 6 7 8 9 10 3 1b
16. BG9719, an A1R antagonist, protects against the decline in renal function observed with diuretic therapy n = 63, NYHA class II-IV, EF 40% and edema despite furosemide (80 mg/d) IV BG9928 (3, 15, 75 y 225 mg) vs placebo for 10 days BG9719 increased urine output, sodium excretion and GFR Furosemide increased urine output at the expense of decreased GFR BG9719 plus furosemide increased diuresis without deterioration in GFR Decrease in body weight of 0.6 kg (0.3 kg with placebo) Gottlieb et al. JACC 2000;35:56-59
17. CKI-201 - ADHF patients with renal impairment Cumulative Urine Volume and daily dose of i.v. furosemide Day 1 Day 2 Day 3 0 40 80 120 160 * Daily dose of i.v. Furosemide (mg) * P < 0.05 vs. placebo). Givertz et al. JACC 2007; 50:1551-1560 By day 4 or day of discharge if earlier, i.v. furosemide administration tended to be lower in the KW-3902 group Placebo 2.5 mg 30 mg 60 mg 15 mg
18. CKI-202 – ADHF patients refractory to diuretics Hourly Urine Volume and Creatinine Clearance (34 ml/min) * P < 0.05 vs. placebo Givertz et al. JACC 2007; 50:1551-1560 Enhances the response to loop diuretics and may have a renal protective effect I ncrease Na + excretion that with "little kaliuresis“ Decreases BW, improves dyspnea and edemas No change in morbidity and mortality for worsening of HF
19. Pilot study 301 patients Barry M. Massie For the PROTECT Investigators and Coordinators
23. PROTECT 60 Day Outcomes: Death and Rehospitalization 1 30 mg vs placebo: HR 0.55 (95% CI = 0.28,1.04) Placebo Rolofylline (n=78) 10 mg (n=74) 20 mg (n=75) 30 mg (n=74) Death or cardiovascular or renal rehospitalization 1 33% 32% 24% 19% Death 10% 12% 8% 5% Rehospitalization for cardiovascular or renal causes 30% 22% 17% 16%
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26. Conclusions • Adenosin harmful in HF • A1 blockade promissing in Acute HF • Protect trial a deception • Drug w real benefit in acute heart failure still missing (and much needed)
Notas del editor
Side effects - GI symptoms and injection site pain at higher doses, which dissipated within minutes after the infusion ended
